Protein kinases related to mitogen activated protein kinase (MAPK or MAP kinase) are part of stress-related signal transduction pathways. p38 MAPK is a serine/threonine kinase that has recently become a target for modulation of cytokine production as it is implicated in multiple signaling pathways activated during inflammation. Inhibitors of p38 MAPK are being studied for treatment of inflammatory diseases such as rheumatoid arthritis, psoriasis and pain.
Alzheimer's Disease (AD) is a progressive and terminal condition characterized by debilitating memory loss and extensive deterioration of cognitive and functional abilities. Currently available therapies for AD are palliative and neither cure nor arrest progression of the disease. Cholinesterase inhibitors such as Razadyne® (galantamine), Exelon® (rivastigmine), Aricept® (donepezil), and Cognex® (tacrine) have been prescribed for early stages of AD, and may temporarily delay or halt progression of symptoms. However, as AD progresses, the brain loses less acetylcholine, thereby rendering cholinesterase inhibitors ineffective. Namenda® (memantine), an N-methyl D-aspartate (NMDA) antagonist, is also prescribed to treat moderate to severe Alzheimer's disease; however only temporary benefits are realized.
There is a need for novel MAP kinase inhibitors. There is also a need for novel treatments for a variety of disease states for which MAP kinase is implicated. There is a further need for novel and effective treatments for neurodegenerative diseases and neurological disorders. In particular, there is a continuing need for treatments of dementia and memory loss associated with Alzheimer's Disease.